Risk Factors of the Development of Diabetes Mellitus After Kidney Transplantation.

BACKGROUND: The occurrence of diabetes mellitus is common after kidney transplantation (posttransplant diabetes mellitus [PTDM]) and enhances the cardiovascular risk and risk for kidney graft loss. The incidence of PTDM is about 5% to 40%. This study aimed to examine the potential risk factors that determine the occurrence of PTDM. METHODS: This study retrospectively included 298 patients from transplantation unit of Evangelismos who underwent kidney transplantation during a 10-year period (January 1, 2009, to January 1, 2019). Kidney transplant recipients with diabetes mellitus prior to transplantation or those with follow-up of <6 months were rejected from the study. In total, the study included 274 recipients with a mean age of 50 ± 18 years. The mean time of monitoring was 63 ± 18 months. The PTDM diagnosis was based on the 2018 criteria of the American Diabetes Association. RESULTS: Of 274 kidney transplant recipients, PTDM developed in 38 (13.8%) patients over a period of 11 ± 9 months after transplantation. Given that immunosuppressive therapy was identical in most patients, statistical analysis did not correlate the incidence of diabetes with treatment. However, there was a correlation for the occurrence of PTDM between the presence of hypomagnesemia and increased uric acid levels. Finally, there was a negative correlation between the age of the recipient and the time of PTDM onset. CONCLUSION: Hypomagnesemia and hyperuricemia increased the risk of PTDM in these patients. Given the association between hypomagnesemia and the development of diabetes mellitus after kidney transplantation, prospective studies are needed to identify the causes of PTDM and to develop prevention strategies.

Determinants of Parathyroid Hormone Levels During the First Year After Kidney Transplantation.

BACKGROUND: Spontaneous remission of secondary hyperparathyroidism after kidney transplantation requires time to occur. The aim of the present study was to investigate factors that may be related to the reduction of parathyroid hormone (PTH) after transplantation as well as the rate of its reduction. METHODS: We studied 81 kidney transplant recipients at our transplantation center between January 2014 and September 2017. The relationship of PTH values during the first year after transplant with renal function, type of kidney graft origin (deceased or living), and delayed renal graft function was examined. Moreover, we determined the correlation of the rate of PTH reduction within the first year with the value of PTH before transplant. RESULTS: Of the total of 81 recipients, 28 (35.1%) were women and 53 (64.8%) were men, with a mean age of 47 ± 11.87 years. At the same time, there was a decrease of PTH by 33% in the first half of the first year after transplantation and by 57% in the second. In addition, a statistically significant correlation of PTH with renal function was found (P = .001), with PTH values decreasing as the glomerular filtration rate increased. Finally, transplants from deceased donors were associated with higher values of PTH, whereas the value of PTH before transplant was positively correlated with the value after it (P = .001). CONCLUSIONS: Secondary hyperparathyroidism, which accompanies end-stage chronic renal failure, usually resolves adequately after transplantation. The determinants of this resolution are the recipient's renal function, the kidney graft origin (deceased), and the pretransplant PTH values.

Resistive Renal Index of the Recipient and its Correlation With the Outcome of Kidney Transplantation at the End of the First Year: Preliminary Results.

BACKGROUND: Renal resistive index (RRI) of ultrasonography is a useful and potent tool for the assessment of patients who have undergone transplantations. The aim of this study was to evaluate the association of RRI with renal function 1 year after transplant. METHODS: We retrospectively evaluated 93 kidney allograft recipients. Data were collected from transplantations performed in our medical center between January 2014 and September 2018. Patients with acute loss of the renal function and renal survival <1 year were excluded from the study. We longitudinally compared the RRI at the first week after transplant and the third month, with estimated glomerular filtration rate (eGFR, by Chronic Kidney Disease Epidemiology Collaboration equation) at the end of the first year of transplantation. RRI was divided into 2 groups (RRI ≤0.80 or >0.80). RESULTS: From the total of 86 recipients, 59 (68.6%) were male recipients and 27 female recipients with a mean age of 48.3 ± 12.1 years. No correlations were found between the first week's RRI with sex and age of both donors and recipients (P > .05). Similarly, the first week's RRI was not correlated with delayed graft function (DGF) and 1-year eGFR after transplant (P > .05). On the contrary, RRI performed at the third month was strongly correlated to DGF and eGFR at the end of the first year. Last but not least, neither higher recipient age nor sex affects the value of resistive index in the third month after transplantation (P < .05). CONCLUSIONS: RRI values <0.80 in the third month after kidney transplantation were related to better annual renal function and a lower incidence of DGF.

Body Mass Index and Kidney Donor Profile Index as Prognostic Markers of the Outcome of Renal Transplantation.

BACKGROUND: The aim of this study was to determine the effects of Kidney Donor Profile Index (KDPI) and body mass index (BMI) of the deceased donor on the kidney allograft outcome 1 year after transplantation. METHODS: We retrospectively studied 98 deceased kidney allograft donors with a mean age of 56 ± 12 years. The donors were divided into 5 groups according to their BMI: Normal ΒΜΙ = 25 (n = 25); ΒΜΙ 25 to 29 = Overweight (n = 33); ΒΜΙ 30 to 34.9 = Obese class I (n = 19); ΒΜΙ 35 to 39 = Obese class ΙΙ (n = 11); and ΒΜΙ >40 = Obese class III (n = 10). We examined the impact of the deceased donor's BMI and KDPI on delayed graft function (DGF) and estimated renal glomerular filtration rate (eGFR) (measured by the Chronic Kidney Disease Epidemiology Collaboration equation) 1 year after transplantation. RESULTS: Donor BMI significantly increased the prevalence of DGF (P = .031), and it was associated with higher cold ischemia time (P = .021). However, there was no significant association between the aforementioned BMI groups and 1-year eGFR (P = 0.57), as deceased grafts from donors with increased BMI (BMI > 40) gained sufficient renal function during the first year of transplantation. Moreover, high KDPI was associated not only with DGF (P = .015), but also with decreased values of eGFR (P = .033). CONCLUSION: In this population, we identified no significant association between donor BMI and long-term clinical outcomes in deceased donor kidney transplants. KDPI, and not ΒΜΙ, of the deceased donor seems to be a good prognostic factor of renal function at the end of the first year after kidney transplant, whereas high BMI and high KDPI markedly induce DGF.

Progression of Albuminuria Among Patients with Type 1 Diabetes Mellitus: A Long Term Observational Follow-up Study.

BACKGROUND: The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up. PATIENTS AND METHODS: A cohort of 84 patients, 18-76 years of age, a median duration of diabetes of 24 years (1-50 years) and a median follow-up duration of 12 years (1-37 years) were included in the study. RESULTS: Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04-7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too. CONCLUSIONS: Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.

Management of Patients with Inflammatory Diseases during the COVID-19 Pandemic.

Patients with various inflammatory diseases of the gastrointestinal tract, skin, liver, kidneys, and musculoskeletal system-connective tissues, often undergo different anti-inflammatory therapies to maintain remission and avoid serious and/or life-threatening complications. Available data so far show an increased rate of hospitalization in such patients during the COVID19 pandemic. The key points of our position statement are summarized below: Patients with inflammatory diseases who receive moderate or high-risk anti-inflammatory therapies might be considered as an increased risk group for severe COVID-19 and appropriate measures should be taken in order to protect them. Initiation of immuno-suppressive/modulatory therapies should be done with caution, taking into account the severity of the underlying inflammatory disease, the type of anti-inflammatory treatment, and the risk of exposure to the SARS-CoV-2 virus. Discontinuation of anti-inflammatory therapies in patients who have not been exposed to or infected with the SARS-CoV-2 virus is not recommended. In patients who become infected with SARS-CoV-2, anti-inflammatory therapies should be discontinued, except in special cases. Specialty physicians should actively participate in the Interdisciplinary Teams caring for patients with inflammatory diseases during COVID19 infection.

Persistent hypokalemia due to a rare mutation in gitelman's syndrome.

Chronic hypokalemia is the main finding in patients with Gitelman's syndrome (GS). GS, a variant of Bartter's syndrome, is an autosomal recessive renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. GS is caused by inactivating mutations in the thiazide-sensitive sodium-chloride cotransporter gene. It is also called the "milder" form of Bartter's syndrome, as patients with GS are usually diagnosed in adulthood during routine investigation. Our objective is to highlight the impact of correct distinction between the causes of hypokalemia on management and the need of long-term follow- up after the restoration of normokalemic status. Herein, we report an asymptomatic 40-year-old male, whose persistent hypokalemia was due to GS. The diagnosis was first established by laboratory tests, and he was treated with low-dose aldosterone antagonists (spironolactone), angiotensin-converting enzyme inhibitors, and potassium and magnesium supplements. Genetic testing confirmed the diagnosis of GS and revealed a rare mutation. We conclude that GS is a rare and real diagnostic and therapeutic challenge, for which a close collaboration between endocrinologists and nephrologists is mandatory, as also the thorough genetic investigation of the mutations associated with this syndrome.

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy.

INTRODUCTION: Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up. AIM: The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN. PATIENTS-METHODS: Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens. RESULTS: Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p = 0.04, respectively. CONCLUSIONS: Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients.

AIMS: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. METHODS AND RESULTS: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. CONCLUSIONS: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Recurrence of crescentic IgA nephropathy after renal transplantation.

IgA nephropathy (IgAN) is one of the most common recurrent glomerulonephritis after renal transplantation. Rarely, it is accompanied with the presence of crescents that leads to rapid deterioration of renal function and graft loss. We present a 54-year-old patient with IgAN that received a cadaveric kidney allograft, but developed biopsy proven recurrent IgAN 7 months after renal transplantation. He was treated with intravenous steroids and angiotensin-converting enzyme inhibitor and remission was achieved. 4 years later, he presented again with heavy proteinuria, hematuria and deterioration of renal function. Allograft biopsy revealed recurrent IgAN with crescents, which was successfully treated with pulse intravenous steroids and six monthly doses of intravenous cyclophosphamide. This regime resulted in long-term sustained remission with a stable functioning graft 3 years later. Although it is not an established treatment as in native kidneys, intravenous cyclophosphamide should probably be considered in kidney transplants with potentially reversible recurrent crescentic IgAN.

A case of severe carbamazepine overdose treated successfully with combined hemoperfusion and hemodialysis technique.

Carbamazepine intoxication manifests as altered mental status ranging from drowsiness to a coma and/or cardiac abnormalities such as sinus tachycardia, prolongation of the QRS interval, ventricular tachycardia, and hypotension. The patient may be agitated, but central nervous system (CNS) depression and presentation with coma is more common and could be lethal. Serious CNS toxicity often requires hemoperfusion and/or hemodialysis (HD). Herein, we present a case of a comatose patient, who was treated with a combination of hemoperfusion and HD in series. Our approach to treat the patient with a combination of hemoperfusion and HD was based on evidence from the literature supporting that the hemoperfusion and HD in series might provide the best clearance of carbamazepine.

Renal outcomes in patients with AL amyloidosis: Prognostic factors, renal response and the impact of therapy.

A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m2 ) and proteinuria (≥5 g/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m2 ) was associated with a 2-year progression to dialysis rate of 0% compared to 9% for a ratio of 31-99 and 35% for a ratio ≥100 (P < .001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2-year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (P = .001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib-based therapy was more effective than lenalidomide-based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival.

Intravascular Lymphoma as an Uncommon Cause of Anasarca.

OBJECTIVES: To report a case of intravascular lymphoma (IVL) in a Caucasian patient who presented with anasarca as his sole clinical sign. MATERIAL AND METHODS: A man presented with anasarca-type oedema and fatigue. After excluding heart failure, hepatic cirrhosis, nephrotic syndrome, hypothyroidism, AL-amyloidosis and adverse drug reaction which can all cause oedema, we turned our attention to capillary permeability disorders. RESULTS: Closer review of the bone marrow aspirate demonstrated haemophagocytic histiocytosis, while core, renal and duodenal biopsies showed a B-cell IVL. CONCLUSION: The differential diagnosis of anasarca, a relatively common clinical sign, should include IVL although the diagnosis may still be challenging. LEARNING POINTS: Anasarca-type oedema is an unusual initial presentation of intravascular lymphoma (IVL) and is normally attributed to capillary permeability disorders.Two clinical forms of IVL have been recognized: a Western form and an Asian variant which is characterized by haemophagocytosis.Patients of Caucasian origin who have the clinical features of the Asian variant of IVL make the diagnosis of this condition even more challenging.

A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis.

In this phase 1/2 study, we explored the feasibility and activity of an oral regimen of lenalidomide with low-dose dexamethasone and low-dose oral cyclophosphamide (RdC) in patients with primary systemic light chain amyloidosis. RdC was given for up to 12 cycles in prespecified cohorts at escalated doses: 13 patients were treated in phase 1 and 24 in phase 2; 65% were previously untreated, and most had renal and/or cardiac involvement and elevated cardiac biomarkers. Lenalidomide 15 mg/d and cyclophosphamide 100 mg/d were further evaluated in phase 2. On intention to treat, 20 (55%) patients achieved a hematologic response, including 3 (8%) complete remissions. Hematologic responses were seen at all dose levels and in 4 of 5 patients who had received bortezomib previously. An organ response was recorded in 22% of patients on intention-to-treat and in 40% of patients who survived at least 6 months. The median time to progression was 10 months and the 2-year survival was 41%. Fatigue, nonneutropenic infections, and rash were the most common toxicities. The results of the present study show that RdC is an oral regimen with activity in primary systemic light chain amyloidosis and may be an additional treatment option, especially for patients with preserved organ function or for patients who cannot receive or who relapse after bortezomib. This study is registered at www.clinicaltrials.gov as NCT00981708.

Sclerosing peritonitis presenting 2 years after renal transplantation in a former CAPD patient.

Sclerosing peritonitis (SP) is a rare but serious complication of peritoneal dialysis (PD), characterized by a fibrous peritoneal thickening. The etiology of this condition remains unknown but is likely to be multifactorial. Patients with SP almost invariably develop ultrafiltration and clearance failure. Although a number of pharmacologic drug treatment options have been tried with various results, surgical treatment and cessation of PD are almost always necessary and transfer to hemodialysis is the only practical option. Despite some evidence supporting the recovery of gastrointestinal function after renal transplantation in such patients, SP may very rarely appear much later after the cessation of PD and even after renal transplantation. We report an interesting case of a former PD patient who 2 years after renal transplantation presented with abdominal discomfort, vomiting, and malnutrition due to SP. Despite the initial conservative treatment, the symptoms persisted and a surgical treatment was decided upon. After that the patient recovered with no further complications. Although the appearance of SP after renal transplantation is extremely rare, it must be included in the differential diagnosis of every case of unexplained malnutrition and abdominal obstruction in a patient with a PD history.

An outbreak of hemodialysis catheter-related bacteremia with sepsis caused by Streptococcus agalactiae in a hemodialysis unit.

BACKGROUND: Rates of invasive group B Streptococcus (GBS; Streptococcus agalactiae) disease in adults are on the rise. Invasive GBS disease can be community- or healthcare-associated. We report an outbreak of GBS catheter-related bacteremia in a hemodialysis (HD) unit. MATERIALS AND METHODS: Two patients undergoing HD at the same outpatient HD unit were admitted on the same day (within a few hours of each other) with catheter-related GBS bacteremia. A retrospective study was undertaken at the HD unit to address risk factors for febrile illness on the last HD session day. A detailed questionnaire was completed by all HD patients treated on the same day as the two GBS patients and by all members of the nursing and medical staff. Medical and nursing records of the HD unit were reviewed, as well as infection control and catheter care practices. Patients and staff members submitted swabs for culture. RESULTS: No rectal or vaginal culture of any HD patient or staff member was positive for GBS. The development of recent febrile disease was significantly associated with the presence of a hemodialysis catheter (p=0.028) and care for more than 30min by a specific nurse during the last two HD sessions (p=0.007). CONCLUSIONS: We speculate that the GBS strain was transmitted from one patient to the other through the hands of medical personnel. No such outbreak has ever been reported in HD patients. The importance of strict infection control practices in HD units and the avoidance of catheters for long-term HD should be emphasized.

Total parathyroidectomy without autotransplantation in dialysis patients and renal transplant recipients, long-term follow-up evaluation.

BACKGROUND: Persistent secondary hyperparathyroidism not responding to medication is treated successfully with surgical excision of parathyroid glands (total parathyroidectomy [PTX]). PTX without autotransplantation of parathyroid glands excludes the risk for recurrence of hyperparathyroidism. METHODS: During the years 2002 to 2005, 36 total parathyroidectomies were performed in 33 patients: 21 dialysis patients because of end-stage renal disease and 12 renal transplant recipients. RESULTS: PTX without autotransplantation was performed successfully in 33 patients, whereas 3 patients were reoperated for remaining parathyroid glands. Immediate improvement of clinical symptoms and a decrease of serum calcium and parathormone levels were observed after surgical procedures. Oral replacement treatment with vitamin D (1a-calcidiol) and calcium was commenced and long-term follow-up evaluation (23.5 +/- 7.6 mo) showed that calcium homeostasis was controlled adequately. CONCLUSIONS: PTX without autotransplantation is a safe and effective surgical procedure for the treatment of resistant secondary hyperparathyroidism with immediate response of clinical symptoms. Replacement treatment with vitamin D and calcium provides satisfactory coverage of individual needs.

Quality of life in the elderly patients on dialysis.

The pattern of end-stage renal disease (ESRD) has changed significantly with the emerging predominance of elderly patients. Age is no longer seen as a contraindication to dialysis. Based on 2004 data, in the USA, patients aged 45-64 years old comprise the largest portion of the incident population, while patients aged 75 and older have the highest incident rates of ESRD. Mortality is higher among the elderly dialysis patients for whom cardiovascular diseases and infections are the most common causes of death. The quality of life (QoL) of these patients has been found to vary in different investigations, dependent on such factors as the investigator(s), the composition of the study group and the criteria used, among others; however, age was always found one of the major determinants of their QoL. Quality-of-life data suggest that older dialysis patients have similar levels of social functioning and mental health as younger dialysis patients but that their level of physical functioning is poorer. As such, the survival and QoL of elderly patients depends mainly on the severity of the comorbid conditions. The rationing of dialysis on the basis of age alone is not justified as dialysis can provide elderly patients with the means to gain the health status that permits them to enjoy life, but in their own way.